The overall objective is to understand collagen metabolism in normal and abnormal wound healing so that human diseases characterized by excessive scar formation (excessive collagen deposition) or inadequate wound strength (inadequate collagen deposition) can be corrected by regulation of collagen metabolism. An animal model for excessive collagen deposition does not exist. However, the human keloid serves as a model where the equilibrium between collagen synthesis and degradation which normally results in a fine line scar has been lost and there is overabundant collagen deposition. Hypotheses formulated from keloid studies are tested in cell culture systems and the normal rat wound model to clarify events in normal and abnormal healing. Having found that the rate of collagen synthesis in keloid is greater than normal skin and that collagen degradation may be inhibited, the inflammatory cells of keloids and healing wounds will be isolated, identified, quantitated and their effects on collagen metabolism tested. Activated macrophages and their exudate alter fibroplasia and this factor will be isolated and compared to a possible similar keloid factor. Keloid collagen being more soluble than normal skin, lysyl oxidase activity may show a cross-linking defect. BAPN will be used to create a cross-linking defect in cell culture and rat wound to study the influence of cross-linking deficiency on collagen synthesis and degradation. Studies will continue on the effects of corticosteroids on collagen synthesis, degradation, inflammation and collagenase inhibitors.